Tumour inflammation signature and expression of S100A12 and HLA class I improve survival in HPV-negative hypopharyngeal cancer

Michael Mints,David Landin,Anders Näsman,Leila Mirzaie,Mark Zupancic,Linda Marklund,Eva Munck-Wikland,Ramona Gabriela Ursu,Torbjörn Ramqvist,Tina Dalianis

doi:10.1038/s41598-020-80226-z

Abstract

Hypopharyngeal squamous cell carcinoma (HPSCC) has a very poor prognosis. Local surgery may increase survival, but is often avoided due to significant post-op co-morbidities. Since prognostic markers are lacking, the aim was to find predictive biomarkers that identify patients whose response to oncological treatment is poor and who may benefit from primary surgery to increase survival. Pretreatment biopsies from 23 HPSCC patients, 3 human papillomavirus (HPV) positive and 20 HPV-negative, were analyzed for expression of 750 mRNAs using the Nanostring nCounter IO360 panel in relation to 3-year survival. Validation was performed through immunohistochemistry (IHC) for HLA class I and S100A12 in 74 HPV-negative HPSCC samples. Clustering identified a subset of HPV-negative HPSCC with favorable prognosis and a gene expression signature overexpressing calgranulins and immune genes, distinct from that of HPV-positive HPSCC. Enrichment analysis showed immune signaling, including the tumor inflammation signature, to be enriched in surviving patients. IHC validation confirmed high S100A12 and HLA class I expression to correlate with survival in HPV-negative HPSCC. This shows that immune activity is strongly related to survival in HPV-negative HPSCC. Enrichment of the tumor inflammation signature indicates a potential benefit of immunotherapy. Low expression of both HLA class I and S100A12 could be used to select patients for local surgery.

Highlights

Hypopharyngeal squamous cell carcinoma (HPSCC) has a very poor prognosis
To identify gene expression related to patient survival when only receiving radiotherapy or chemoradiotherapy, tumors from patients receiving local surgery were excluded, as were patients who died of causes other than HPSCC within 3 years (Table 1)
Samples could be divided into four clusters; human papillomavirus (HPV)-positive samples formed one cluster, while HPV-negative samples divided into three groups with high, intermediate and low proportions of survivors, respectively (Fig. 1A)

Summary

Introduction

Hypopharyngeal squamous cell carcinoma (HPSCC) has a very poor prognosis. Local surgery may increase survival, but is often avoided due to significant post-op co-morbidities. Enrichment of the tumor inflammation signature indicates a potential benefit of immunotherapy Low expression of both HLA class I and S100A12 could be used to select patients for local surgery. Predictive and prognostic biomarkers are needed to optimize treatment for patients with limited as well as locoregionally advanced tumors, and in the metastatic setting where the objective treatment response rate is approximately 20%, it is important to avoid unnecessary toxicity in patients who will not respond The aim of this investigation was to find prognostic/predictive biomarkers enabling identification of patients with poor prognosis after oncological treatment. For this purpose, mRNA expression in HPSCC biopsies was evaluated in relation to patient survival using the PanCancer IO 360 panel. The expression of two putative biomarkers identified during the initial analysis, S100A12 and HLA class I, was validated to correlate with survival through immunohistochemistry (IHC)

Methods

Results

Conclusion